The role of carnitine in intracellular metabolism.

In animal cells long chain fatty acids are transferred into the mitochondria for oxidation as acylcarnitines. Carnitine palmitoyltransferase I in the outer membrane, and carnitine translocase plus carnitine palmitoyltransferase II in the inner membrane catalyse the transfer. Carnitine palmitoyltransferase I is inhibited by malonyl-CoA, an intermediate in fatty acid synthesis. In the liver of fasted, diabetic, or thyreotoxic animals this enzyme shows increased activity and less inhibition by malonyl-CoA. Peroxisomes also contain carnitine acyltransferases and a beta-oxidation enzyme system. This system is particularly active in the shortening of very long chain fatty acids. The carnitine acyltransferases of the peroxisomes presumably are active in the transfer of the shortened acyl-CoAs and the acetyl-CoA to the mitochondria for complete oxidation. The carnitine acyltransferases of the mitochondria can catalyse the formation of propionylcarnitine and branched chain acylcarnitines from branched chain amino acids, and methylthiopropionylcarnitine from methionine. Their formation may represent a "security valve" preventing acyl-CoA accumulation in the mitochondria. The liver, which normally releases carnitine for other tissues, releases the branched chain acylcarnitines even more easily. This may be important for the development of secondary carnitine deficiency in some inborn errors of metabolism which are accompanied by the accumulation of acyl-CoAs in the tissue.